10-6485181-G-A

Variant names:

• chr10-6485181-G-A
• rs2236379
• NM_006257.5:c.989C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006257.5(PRKCQ):​c.989C>T​(p.Pro330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,612,426 control chromosomes in the GnomAD database, including 65,086 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.30 (7246 hom., cov: 31)
  • Exomes 𝑓: 0.27 (57840 hom.)
• Consequence: PRKCQ NM_006257.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2 B:2
• Conservation: PhyloP100: 0.729
• Publications: 48 publications found

Genes affected

PRKCQ (HGNC:9410): (protein kinase C theta) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors. [provided by RefSeq, Jul 2008]

ENSG00000302067 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.043051E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	NM_006257.5	MANE Select	c.989C>T	p.Pro330Leu	missense	Exon 10 of 18	NP_006248.1
	PRKCQ	NM_001323265.1		c.989C>T	p.Pro330Leu	missense	Exon 10 of 18	NP_001310194.1
	PRKCQ	NM_001282644.2		c.881C>T	p.Pro294Leu	missense	Exon 10 of 18	NP_001269573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCQ	ENST00000263125.10	TSL:1 MANE Select	c.989C>T	p.Pro330Leu	missense	Exon 10 of 18	ENSP00000263125.5
	PRKCQ	ENST00000397176.6	TSL:5	c.989C>T	p.Pro330Leu	missense	Exon 10 of 17	ENSP00000380361.2
	PRKCQ	ENST00000539722.5	TSL:2	c.614C>T	p.Pro205Leu	missense	Exon 9 of 17	ENSP00000441752.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45614 AN: 151740 Hom.: 7250 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.305 AC: 76764 AN: 251410 AF XY: 0.305

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.414

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.274 AC: 400411 AN: 1460568 Hom.: 57840 Cov.: 33 AF XY: 0.277 AC XY: 201607 AN XY: 726630

African (AFR) AF: 0.366 AC: 12254 AN: 33462

American (AMR) AF: 0.378 AC: 16899 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6647 AN: 26108

East Asian (EAS) AF: 0.440 AC: 17445 AN: 39676

South Asian (SAS) AF: 0.431 AC: 37124 AN: 86194

European-Finnish (FIN) AF: 0.196 AC: 10447 AN: 53344

Middle Eastern (MID) AF: 0.307 AC: 1771 AN: 5762

European-Non Finnish (NFE) AF: 0.252 AC: 280345 AN: 1110990

Other (OTH) AF: 0.290 AC: 17479 AN: 60330

GnomAD4 genome AF: 0.300 AC: 45628 AN: 151858 Hom.: 7246 Cov.: 31 AF XY: 0.302 AC XY: 22403 AN XY: 74210

African (AFR) AF: 0.363 AC: 15033 AN: 41364

American (AMR) AF: 0.351 AC: 5361 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 876 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2165 AN: 5138

South Asian (SAS) AF: 0.437 AC: 2099 AN: 4806

European-Finnish (FIN) AF: 0.198 AC: 2091 AN: 10546

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17107 AN: 67944

Other (OTH) AF: 0.295 AC: 624 AN: 2112

Alfa AF: 0.271 Hom.: 21287

Bravo AF: 0.313

TwinsUK AF: 0.244 AC: 905

ALSPAC AF: 0.259 AC: 1000

ESP6500AA AF: 0.348 AC: 1535

ESP6500EA AF: 0.250 AC: 2147

ExAC AF: 0.305 AC: 36980

Asia WGS AF: 0.407 AC: 1418 AN: 3478

EpiCase AF: 0.262

EpiControl AF: 0.260

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Inflammatory bowel disease 1 Pathogenic:2

Lab of Gastroenterology, College of Medicine, First Affiliate Hospital of Zhejiang University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

Jul 30, 2025

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30828974)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.2
DANN	Benign	0.32
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.00080	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.35	N
PhyloP100		0.73
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Benign	0.35	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.47
ClinPred		0.0026	T
GERP RS		-2.7
Varity_R		0.026
gMVP		0.18
Mutation Taster		=94/6	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2236379; hg19: chr10-6527143; COSMIC: COSV54105779;